US3992410A - Process for manufacturing thiophene derivatives - Google Patents

Process for manufacturing thiophene derivatives Download PDF

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Publication number
US3992410A
US3992410A US05/583,764 US58376475A US3992410A US 3992410 A US3992410 A US 3992410A US 58376475 A US58376475 A US 58376475A US 3992410 A US3992410 A US 3992410A
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US
United States
Prior art keywords
hydrogen
formula
acid
group
lower alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US05/583,764
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English (en)
Inventor
David Boyd Baird
Brian Ribbons Fishwick
Ian Knowles Barben
John Murray Holland, deceased
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Imperial Chemical Industries Ltd
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Imperial Chemical Industries Ltd
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Publication date
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Publication of US3992410A publication Critical patent/US3992410A/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/66—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/72—Benzo[c]thiophenes; Hydrogenated benzo[c]thiophenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings

Definitions

  • This invention relates to a process for the manufacture of salts of 2-aminothiophenes.
  • R, X and Y are each independently a hydrogen atom, an alkyl radical or an optionally substituted aryl radical, or a thienyl or furyl radical or either R and X or X and Y 1 together form a chain of methylene groups to form a 5- or 6-membered fused ring system, which comprises treating the corresponding compound of the formula: ##STR1## with hydrogen sulphide in the presence of an acid and in the presence of an organic solvent.
  • the alkyl radicals represented by R, X and Y are preferably lower alkyl radicals containing from 1 to 4 carbon atoms such as methyl, ethyl, propyl and butyl radicals.
  • the optionally substituted aryl radicals are preferably optionally substituted phenyl radicals such as phenyl, tolyl, xylyl, chlorophenyl, bromophenyl, nitrophenyl, methoxyphenyl, ethoxyphenyl, methoxycarbonylphenyl, ethoxycarbonylphenyl, lower alkylcarbonylphenyl such as acetylphenyl, cyanophenyl, lower alkylsulphonylphenyl such as methylsulphonylphenyl, carbamoylphenyl and sulphamoylphenyl and N-lower alkyl and N:N-di(lower alkyl)derivatives thereof.
  • Y represents hydrogen.
  • X preferably represents methyl and, above all, hydrogen.
  • R represents hydrogen, and, above all, optionally substituted phenyl.
  • the process of the invention can be conveniently carried out by passing a stream of gaseous hydrogen sulphide through a solution of the compound of Formula I in an organic solvent which also contains the acid, the reaction being carried out at a temperature between -20° C and the boiling point of the reaction medium.
  • the resulting salt of the 2-aminothiophene is isolated by conventional methods, for example by dilution with an organic liquid in which the salt is insoluble.
  • the organic solvent used for the reaction medium is one in which the said salt is substantially insoluble, so that the said salt separates out as it is formed and can be directly isolated by filtration.
  • organic solvents there may be mentioned hydrocarbons such as toluene, esters such as ethyl acetate, ketones such as acetone, alcohols such as n-butanol, isopropanol, ethanol and methanol, ethers such as dioxan, tetrahydrofuran, liquid carboxylic acids such as acetic acid, and polar aprotic solvents such as dimethylformamide.
  • hydrocarbons such as toluene
  • esters such as ethyl acetate
  • ketones such as acetone
  • alcohols such as n-butanol, isopropanol
  • ethers such as dioxan, tetrahydrofuran
  • liquid carboxylic acids such as acetic acid
  • polar aprotic solvents such as dimethylformamide
  • the amount of acid present in the reaction is not critical provided that at least one mole of acid is used for each mole of the compound of Formula I.
  • the acids used in the reaction are strong acids having a negative pKa value, and as examples of such acids there may be mentioned hydrogen chloride, hydrogen bromide, sulphuric acid and benzene sulphonic acid.
  • the compounds of Formula I used in the process are aldehydes or ketones depending on whether or not R is a hydrogen atom, but if desired such compounds can be used in the form of their reaction products with alcohols, i.e. the corresponding ketals or acetals, which are reconverted to the parent aldehyde or ketone during the reaction.
  • the salts of the 2-aminothiophenes produced by the process of the invention are valuable as diazo components in the production of azo dyestuffs.
  • the said salts can be converted to other thiophene derivatives in conventional manner.
  • they can be converted to 2-acylamino derivatives by treatment with an acylatling agent such as acetic anhydride in the presence of a base, and such reactions can be carried out, if desired, without intermediate isolation of the said salt from the reaction mixture of the present process.
  • an acylatling agent such as acetic anhydride
  • a slow stream of hydrogen chloride gas is bubbled for 10 minutes through a solution of 13.7 parts of 2-oxo-cyclohexylacetonitrile in 100 parts of methanol at 0° to 10° C.
  • a slow stream of hydrogen sulphide gas is then bubbled through the mixture for 8 hours at 0° to 10° C.
  • the mixture is then allowed to stand at room temperature andthe hydrochloride of 2-amino-4:5:6:7-tetrahydrobenzo-b-thiophene which separates out is filtered off and dried.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US05/583,764 1974-06-11 1975-06-04 Process for manufacturing thiophene derivatives Expired - Lifetime US3992410A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
UK25847/74 1974-06-11
GB2584774A GB1470542A (en) 1974-06-11 1974-06-11 Process for manufacturing salts of 2-aminothiophenes

Publications (1)

Publication Number Publication Date
US3992410A true US3992410A (en) 1976-11-16

Family

ID=10234316

Family Applications (1)

Application Number Title Priority Date Filing Date
US05/583,764 Expired - Lifetime US3992410A (en) 1974-06-11 1975-06-04 Process for manufacturing thiophene derivatives

Country Status (8)

Country Link
US (1) US3992410A (is")
JP (1) JPS518263A (is")
CH (1) CH596203A5 (is")
DE (1) DE2526086A1 (is")
ES (1) ES438436A1 (is")
FR (1) FR2274623A1 (is")
GB (1) GB1470542A (is")
IT (1) IT1038162B (is")

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6492413B2 (en) 1993-01-15 2002-12-10 G.D. Searle & Co. 3.4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2570083A (en) * 1947-04-14 1951-10-02 Standard Oil Dev Co Production of thiophene from diolefin and hydrogen sulfide

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2570083A (en) * 1947-04-14 1951-10-02 Standard Oil Dev Co Production of thiophene from diolefin and hydrogen sulfide

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6492413B2 (en) 1993-01-15 2002-12-10 G.D. Searle & Co. 3.4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents
US20030013744A1 (en) * 1993-01-15 2003-01-16 G.D. Searle & Co. 3,4-diaryl thiophenes and analogs thereof having use as anti-inflammatory agents
US6599934B1 (en) 1993-01-15 2003-07-29 G.D. Searle & Co. 3,4-diaryl thiopenes and analogs thereof having use as antiinflammatory agents
US20030153602A1 (en) * 1993-01-15 2003-08-14 G.D. Searle & Co. 3,4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents
US7030153B2 (en) 1993-01-15 2006-04-18 G.D. Searle & Co. 3,4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents

Also Published As

Publication number Publication date
GB1470542A (en) 1977-04-14
JPS518263A (en) 1976-01-23
IT1038162B (it) 1979-11-20
DE2526086A1 (de) 1976-01-08
FR2274623A1 (fr) 1976-01-09
CH596203A5 (is") 1978-03-15
FR2274623B1 (is") 1979-01-19
ES438436A1 (es) 1977-02-01

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